Imipenem monohydrate, the crystalline monohydrate of N-formimidoyl derivative of thienamycin of Formula I, is the first clinically available member of a new class of β-lactam antibiotic that possess the carbapenem ring system. Imipenem exhibits an extremely broad spectrum of activity against gram-positive and gram-negative aerobic and anaerobic species, which is partly due to its high stability in presence of β-lactamases.
Imipenem was initially obtained by lyophilization technique as disclosed in U.S. Pat. No. 4,194,047. An alternate process of freeze crystallization or lyophilization has been reported by M. Connolly et. al in J. Pharm. Sci, 85, 174–175 (1996). However, lyophilized product so obtained is often found to be largely amorphous which is thermodynamically unstable. A crystalline monohydrate form of imipenem is disclosed in U.S. Pat. No. 4,260,543, which is obtained by crystallization of a lyophilized sample of imipenem and was found to have unexpected stability in the solid state over the lyophilized form (amorphous form). However, it is reported that the changes in lyophilization conditions can change the degree of crystallinity of the final product. Crystallinity is of interest in the study of lyophilized imipenem because crystalline imipenem is more thermodynamically stable than amorphous or disordered imipenem. Processes of obtaining crystalline imipenem as described in the prior art requires specialized equipment such as freeze dryer or a lyophilizer which renders it unattractive at a commercial scale and also do not produce the product having consistent degree of crystallinity.